Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.
Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Molecules. 2020 Dec 31;26(1):147. doi: 10.3390/molecules26010147.
-methyladenosine(mA) is the most abundant modification in mRNA. Studies on proteins that introduce and bind mA require the efficient synthesis of oligonucleotides containing mA. We report an improved five-step synthesis of the mA phosphoramidite starting from inosine, utilising a 1--benzotriazol-1-yloxytris(dimethylamino)phosphoniumhexafluorophosphate (BOP)mediated SAr reaction in the key step. The route manifests a substantial increase in overall yield compared to reported routes, and is useful for the synthesis of phosphoramidites of other adenosine derivatives, such as ethanoadenosine, an RNA analogue of the DNA adduct formed by the important anticancer drug Carmustine.
甲基腺嘌呤（mA）是 mRNA 中最丰富的修饰。研究引入和结合 mA 的蛋白质需要高效合成含有 mA 的寡核苷酸。我们报告了一种从肌苷开始的改进的五步合成 mA 亚磷酰胺的方法，该方法在关键步骤中利用 1--苯并三唑-1-基氧基三（二甲氨基）膦六氟磷酸盐（BOP）介导的 SAr 反应。与报道的路线相比，该路线的总收率显著提高，并且可用于合成其他腺嘌呤衍生物的亚磷酰胺，例如乙氧基腺嘌呤，它是抗癌药物卡莫司汀形成的 DNA 加合物的 RNA 类似物。
